Heparanase regulates the M1 polarization of renal macrophages and their crosstalk with renal epithelial tubular cells after ischemia/reperfusion injury

Gisella Vischini, Giovanni Gambaro, Valentina Masola, Gianluigi Zaza, Gloria Bellin, Luigi Dall'Olmo, Simona Granata, Maria Francesca Secchi, Antonio Lupo, Maurizio Onisto

Risultato della ricerca: Contributo in rivistaArticolo in rivista

23 Citazioni (Scopus)

Abstract

Heparanase (HPSE) is part of the biologic network triggered by ischemia/reperfusion (I/R) injury, a complication of renal transplantation and acute kidney injury. During this period, the kidney or graft undergoes a process ofmacrophages recruitment andactivation.HPSE may therefore control these biologic effects. We measured the ability of HPSE and its inhibitor, SST0001, to regulate macrophage polarization and the crosstalk between macrophages and HK-2 renal tubular cells during in vitro hypoxia/reoxygenation (H/R). Furthermore, we evaluated in vivo renal inflammation, macrophage polarization, and histologic changes in mice subjected to monolateral I/R and treated with SST0001 for 2 or 7 d. The in vitro experiments showed that HPSE sustained M1 macrophage polarization and modulated apoptosis, the release of damage associated molecular patterns in post-H/R tubular cells, the synthesis of proinflammatory cytokines, and the up-regulation of TLRs on both epithelial cells and macrophages. HPSE also regulated M1 polarization induced by H/R-injured tubular cells and the partial epithelial-mesenchymal transition of these epithelial cells byM1macrophages.All these effectswere prevented by inhibiting HPSE. Furthermore, the inhibition of HPSE in vivo reduced inflammation andM1 polarization in mice undergoing I/R injury, partially restored renal function and normal histology, and reduced apoptosis. These results show for the first time that HPSE regulates macrophage polarization as well as renal damage and repair after I/R. HPSE inhibitors could therefore provide a new pharmacologic approach to minimize acute kidney injury and to prevent the chronic profibrotic damages inducedby I/R.-Masola,V.,Zaza,G.,Bellin,G.,Dall'Olmo,L.,Granata,S., Vischini, G., Secchi, M. F., Lupo, A., Gambaro, G., Onisto, M. Heparanase regulates the M1 polarization of renal macrophages and their crosstalk with renal epithelial tubular cells after ischemia/reperfusion injury. FASEB J. 32, 742-756 (2018). www.fasebj.org.
Lingua originaleEnglish
pagine (da-a)742-756
Numero di pagine15
RivistaTHE FASEB JOURNAL
Volume32
DOI
Stato di pubblicazionePubblicato - 2018

Keywords

  • Biochemistry
  • Biotechnology
  • Cytokines
  • Genetics
  • Inflammation
  • Kidney
  • Molecular Biology
  • SST0001

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